PDBsum entry 5ncw

Hydrolase

PDB id: 5ncw

Contents

Protein chains

334 a.a.

33 a.a.

Ligands

TRS

GOL ×2

Metals

_ZN ×2

__K

IOD ×4

_CL ×6

Waters ×474

PDB id:

5ncw

Name:

Hydrolase

Title:

Structure of the trypsin induced serpin-type proteinase inhibitor, miropin (v367k/k368a mutant).

Structure:

Serpin-type proteinase inhibitor, miropin. Chain: a. Engineered: yes. Mutation: yes. Other_details: the amino-terminal amino acid residues (gplgs) are coming from the cloning strategy.. Serpin-type proteinase inhibitor, miropin. Chain: b. Engineered: yes.

Source:

Tannerella forsythia. Organism_taxid: 28112. Gene: bfo_3114. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: rosetta. Expression_system_variant: rosetta

Resolution:

1.50Å R-factor: 0.163 R-free: 0.183

Authors:

T.Goulas,M.Ksiazek,I.Garcia-Ferrer,D.Mizgalska,J.Potempa,X.Gomis-Ruth

Key ref:

T.Goulas et al. (2017). A structure-derived snap-trap mechanism of a multispecific serpin from the dysbiotic human oral microbiome. J Biol Chem, 292, 10883-10898. PubMed id: 28512127

Date:

06-Mar-17 Release date: 24-May-17

Protein chain

G8UQY8  (G8UQY8_TANFA) -  Serpin from Tannerella forsythia (strain ATCC 43037 / JCM 10827 / CCUG 21028 A / KCTC 5666 / FDC 338)

Seq: 432 a.a.

Struc: 334 a.a.*

Protein chain

G8UQY8  (G8UQY8_TANFA) -  Serpin from Tannerella forsythia (strain ATCC 43037 / JCM 10827 / CCUG 21028 A / KCTC 5666 / FDC 338)

Seq: 432 a.a.

Struc: 33 a.a.

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

J Biol Chem 292:10883-10898 (2017)

PubMed id: 28512127

A structure-derived snap-trap mechanism of a multispecific serpin from the dysbiotic human oral microbiome.

T.Goulas, M.Ksiazek, I.Garcia-Ferrer, A.M.Sochaj-Gregorczyk, I.Waligorska, M.Wasylewski, J.Potempa, F.X.Gomis-Rüth.

ABSTRACT

Enduring host-microbiome relationships are based on adaptive strategies within a particular ecological niche.Tannerella forsythiais a dysbiotic member of the human oral microbiome that inhabits periodontal pockets and contributes to chronic periodontitis. To counteract endopeptidases from the host or microbial competitors,T. forsythiapossesses a serpin-type proteinase inhibitor called miropin. Although serpins from animals, plants, and viruses have been widely studied, those from prokaryotes have received only limited attention. Here we show that miropin uses the serpin-type suicidal mechanism. We found that, similar to a snap trap, the protein transits from a metastable native form to a relaxed triggered or induced form after cleavage of a reactive-site target bond in an exposed reactive-center loop. The prey peptidase becomes covalently attached to the inhibitor, is dragged 75 Å apart, and is irreversibly inhibited. This coincides with a large conformational rearrangement of miropin, which inserts the segment upstream of the cleavage site as an extra β-strand in a central β-sheet. Standard serpins possess a single target bond and inhibit selected endopeptidases of particular specificity and class. In contrast, miropin uniquely blocked many serine and cysteine endopeptidases of disparate architecture and substrate specificity owing to several potential target bonds within the reactive-center loop and to plasticity in accommodating extra β-strands of variable length. Phylogenetic studies revealed a patchy distribution of bacterial serpins incompatible with a vertical descent model. This finding suggests that miropin was acquired from the host through horizontal gene transfer, perhaps facilitated by the long and intimate association ofT. forsythiawith the human gingiva.